RT Journal Article
SR Electronic
T1 Dynorphins other than dynorphin A(1-17) lack spinal antianalgesic activity but do act on dynorphin A(1-17) receptors.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1073
OP 1080
VO 259
IS 3
A1 Rady, J J
A1 Fujimoto, J M
A1 Tseng, L F
YR 1991
UL http://jpet.aspetjournals.org/content/259/3/1073.abstract
AB In recent publications we have proposed that dynorphin (Dyn) A(1-17) functions as an antianalgesic modulator to oppose opioid-induced antinociception in mice. In the present experiments using the tail-flick response in mice, other Dyns [Dyn A(1-8), Dyn A(1-13), Dyn A(2-17), Dyn B and alpha- and beta-neoendorphin] when administered intrathecally (i.t.) were shown not to have antianalgesic activity even at high doses (0.5-1 pmol). These Dyns, i.t., did not antagonize the antinociception produced by physostigmine administered i.c.v. or morphine given i.t. These Dyns lacked the intrinsic antianalgesic activity of Dyn A(1-17). However, they had affinity for Dyn A(1-17) receptors as shown in several ways. 1) The antagonism of physostigmine antinociception produced by Dyn A(1-17) given i.t. was reversed by these Dyns given together with Dyn A(1-17). 2) The effect of endogenously released Dyn A(1-17) was reversed. Administered i.c.v., clonidine simultaneously activates antinociceptive and antianalgesic systems [latter mediated spinally by Dyn A(1-17) release]. Thus, these Dyns given i.t. inhibited the action of endogenously released Dyn A(1-17) and allowed the full manifestation of the antinociceptive action of clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)